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A small clinical trial suggests that drugs like Ozempic could be used not only for diabetes and weight loss, but also to protect the brain, slowing the rate at which people with Alzheimer’s lose their ability to think clearly, remember things and carry out daily activities. The findings need to be confirmed in larger trials, which are already underway, before the drugs can be approved for the disease.
The study, conducted in 204 people with Alzheimer’s disease in the UK, found that those taking the diabetes drug liraglutide – an older drug in Ozempic’s class of drugs known as GLP-1 receptor agonists – had 18% slower cognitive decline over a year compared with those taking a placebo.
The trial’s primary goal of changing the rate at which the brain metabolizes glucose, however, was not met, which researchers say may be due to the small size of the study. The results were presented Tuesday at the Alzheimer’s Association International Conference in Philadelphia and have not yet been published in a peer-reviewed journal.
“We’ve known for some time from animal work that GLP-1 has a different type of activity in the brain,” said Dr. Maria Carrillo, chief scientific officer and chief medical affairs officer for the Alzheimer’s Association, who was not involved in the research. “This study really shows us the possibilities that are out there.”
In addition to the cognitive benefits, the study found that the drug was associated with 50% less volume loss in several areas of the brain, according to a news release from the Alzheimer’s Association. Those results raise hopes that larger trials by Ozempic’s maker, Novo Nordisk, will be successful, Carrillo told CNN.
Beyond Diabetes and Weight Loss
The use of GLP-1 drugs has exploded in recent years for diabetes and weight loss, and they have shown benefits for a wide range of other health issues, such as protecting the heart and kidneys, reducing sleep apnea and potentially helping with drug addiction.
Animal studies have suggested that in the brain, the drugs can reduce neuroinflammation, dampen toxic proteins called amyloid and tau, improve insulin resistance and increase synaptic function, or the transmission of impulses between cells, said Dr. Paul Edison, professor of neuroscience at Imperial College London, who led the trial.
“This is the first study that has actually looked at a relatively large number of patients to see if there is a neuroprotective effect in Alzheimer’s disease,” Edison said.
The trial enrolled primarily people with mild Alzheimer’s disease, as measured by a test known as the Mini-Mental State Examination, a scale that ranges up to 30. People with a score of 21 to 26 are considered to have mild Alzheimer’s disease, and the majority of participants in this study had a score of about 22, although some had scores as low as 17, indicating moderate Alzheimer’s disease, Edison said.
Diabetic patients were excluded in an attempt to control for the effects of this disease, which is itself a risk factor for Alzheimer’s disease.
Edison and his team conducted the trial using liraglutide, a daily injection sold under the brand names Victoza for diabetes and Saxenda for weight loss, because it is similar to the GLP-1 hormone found in humans, he said, and it was on the market for diabetes when the study began about a decade ago.
Ozempic, which uses the active ingredient semaglutide, was approved in the US for diabetes in 2017 and then in the UK, and its weight loss counterpart, Wegovy, was approved in the US in 2021. They are given as injections once a week.
The GLP-1 class of drugs also includes Eli Lilly’s Mounjaro and Zepbound, which use the active ingredient tirzepatide, which mimics not only the GLP-1 hormone but also another hormone called GIP. And a growing number of other companies are trying to develop even more powerful drugs. Existing drugs are already in short supply as companies try to meet growing demand.
Lilly is already active in Alzheimer’s disease, with approval this month of a treatment called Kisunla that clears amyloid plaque buildup in the brain. But it has not announced any clinical trials of its GLP-1 drugs in Alzheimer’s.
Lilly told CNN that it “continues to evaluate future development options for tirzepatide but has not announced development plans for Alzheimer’s disease at this time.”
Novo Nordisk, which markets liraglutide and semaglutide, has portrayed its Alzheimer’s trials as a risky bet. Its CEO, Lars Fruergaard Jorgensen, told CNN last year that “Alzheimer’s is one of the most difficult diseases to study, and the list of drug development failures is long.”
“So I just want to warn you,” he continued, “that this is probably the riskiest test we’ve ever undertaken.”
Novo Nordisk is conducting its trials using a daily pill form of semaglutide, with results expected as early as fall 2025. An oral form is already marketed for diabetes under the brand name Rybelsus.
When the studies were announced in 2020, the Danish pharmaceutical giant said it planned to enroll about 3,700 people with early-stage Alzheimer’s disease, with a primary treatment period of about two years.
The company said in a subsequent presentation to investors that its decision to launch the phase three trials was based on data including real-world evidence studies showing lower risks of dementia in people taking GLP-1 drugs, analyses of effects seen in other clinical trials, and animal studies showing the drugs are associated with improved memory function, reduced neuroinflammation and systemic anti-inflammatory effects.
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Earlier this month, a study by researchers at the University of Oxford of U.S. patient records found that semaglutide was associated with a lower risk of cognitive problems and nicotine addiction. The study was designed to assess whether the drug could have negative effects on the brain, and instead found the opposite.
GLP-1 drugs may have However, side effects, including gastrointestinal disturbances such as nausea and vomiting, have been observed. In the clinical trial of liraglutide in patients with Alzheimer’s disease, these effects were the most common.
The study received funding from Novo Nordisk, in addition to the Alzheimer’s Society UK and others.
While more work needs to be done to prove that GLP-1 drugs could help people with Alzheimer’s, Carrillo touted the potential to use these drugs not only alone, but potentially in combination with recently approved drugs that clear amyloid plaque buildup in the brain.
“There is a lot of hope, not only for a positive trial of semaglutide, but also for the possibility of combining it with a monoclonal antibody that is approved today by the FDA,” she said.